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Toxicology Mechanisms and Methods Jan 2022Silica nanoparticles (SiNPs) have been widely used in nanotechnology, and more attention has been paid to their safety evaluation. However, there are still inconsistent... (Meta-Analysis)
Meta-Analysis
Silica nanoparticles (SiNPs) have been widely used in nanotechnology, and more attention has been paid to their safety evaluation. However, there are still inconsistent conclusions about the genotoxicity of SiNPs. A systematic review was conducted to explore whether SiNPs have genotoxicity followed by a meta-analysis of and murine genotoxicity tests. A total of 26 eligible studies were identified in this meta-analysis through a detailed process of inclusion and exclusion, which included 9 studies, 15 studies, and 2 in both. The results of studies showed that SiNPs exposure significantly increased the indicators of the comet assay, such as tail DNA content (T DNA%), tail length (TL), and olive tail moment (OTM). Indicators of mutagenicity had not been affected studies, such as mutation frequency (MF) and micronucleus (MN) frequency. There was a significant increase in MN frequency, but there was no influence on T DNA% . Results of subgroup analysis indicated that size and treatment time of SiNPs were the associated factors genotoxicity. The size of SiNPs, <21 nm, induced more DNA damage than larger sized SiNPs. It could induce MN formation when the treatment time of SiNPs was <12 h, and even more DNA damage when the exposure time over 12 h. SiNPs can induce genotoxicity both and . Comet assay may be more sensitive to detect genotoxicity, and MN frequency may be more suitable to detect genotoxicity.
Topics: Animals; Comet Assay; DNA Damage; Mice; Nanoparticles; Nanotechnology; Silicon Dioxide
PubMed: 34350812
DOI: 10.1080/15376516.2021.1965277 -
Dento Maxillo Facial Radiology Feb 2022To evaluate, through a systematic review (SR) with meta-analysis, the occurrence of genotoxic effects in the oral epithelium after the exposure of patients to panoramic... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate, through a systematic review (SR) with meta-analysis, the occurrence of genotoxic effects in the oral epithelium after the exposure of patients to panoramic radiographs.
METHODS
An SR was performed with the PICOS (Population, Intervention, Comparison, Outcome, and Study design) strategy, aiming to answer the following question: "Can panoramic radiographs induce genotoxic effects on the oral epithelium?" The study was registered in the PROSPERO (International prospective register of systematic reviews) platform. A systematic search was performed in the following electronic databases: PubMed (including MedLine), Scopus, Embase, LILACS, Medline EbscoHost, and Google Scholar. Treatment effects were defined as standardized mean difference (SMD), and 95% confidence intervals (CI) were established. The Joanna Briggs Institute questionnaire for observational studies was applied to assess the risk of bias. The GRADE tool was used to assess the quality of evidence of the SR.
RESULTS
A total of 251 potentially relevant studies were selected through the search strategy. After screening titles and abstracts, 11 full-text manuscripts were assessed for eligibility and nine observational studies were included in the meta-analysis. The present study showed an increase in micronuclei after the exposure (SMD = 0.21, 95% CI, 0.03 to 0.28, = 0.02), with a Tauindex = 0.00, Chi = 2.35, and -value = 0.97. Therefore, the articles selected were considered homogeneous and the I² of 0% indicated low heterogeneity.
CONCLUSION
According to the studies analysed, although the quality of evidence was considered low, panoramic radiographs can cause genotoxic damage in the oral epithelium but with a small effect size.
Topics: DNA Damage; Epithelium; Humans; Radiography, Panoramic
PubMed: 34319790
DOI: 10.1259/dmfr.20210149 -
Mutation Research. Reviews in Mutation... 2021Micronucleus (MN) assay has been widely used as a biomarker of DNA damage, chromosomal instability, cancer risk and accelerated aging in many epidemiological studies. In... (Meta-Analysis)
Meta-Analysis Review
Micronucleus (MN) assay has been widely used as a biomarker of DNA damage, chromosomal instability, cancer risk and accelerated aging in many epidemiological studies. In this narrative review and meta-analysis we assessed the association between lymphocyte micronuclei (MNi) and cancers of the skin, blood, digestive tract, and prostate. The review identified nineteen studies with 717 disease subjects and 782 controls. Significant increases in MRi for MNi were observed in the following groups: subjects with blood cancer (MRi = 3.98; 95 % CI: 1.98-7.99; p = 0.000) and colorectal cancer (excluding IBD) (MRi = 2.69; 95 % CI: 1.82-3.98, p < 0.000). The results of this review suggest that lymphocyte MNi are a biomarker of DNA damage and chromosomal instability in people with haematological or colorectal cancers. However, the MRi for lymphocyte MNi in subjects with cancers of skin, prostate, esophagus was not significantly increased. More case-control and prospective studies are warranted to further verify the observed trends and to better understand the role of lymphocyte MNi as a biomarker of cancer risk in blood, skin, digestive tract and prostate.
Topics: Chromosomal Instability; Colorectal Neoplasms; DNA Damage; Esophageal Neoplasms; Humans; Male; Micronucleus Tests
PubMed: 34083057
DOI: 10.1016/j.mrrev.2021.108372 -
Mutation Research. Reviews in Mutation... 2021Coronary artery disease (CAD) is the leading cause of morbidity and mortality worldwide. Coronary angiography allows an accurate assessment of the extent and severity of... (Meta-Analysis)
Meta-Analysis
Coronary artery disease (CAD) is the leading cause of morbidity and mortality worldwide. Coronary angiography allows an accurate assessment of the extent and severity of atherosclerotic coronary narrowing, but it provides little characterization of early detection of potentially asymptomatic vulnerable plaque. The identification of the coronary "vulnerable patient" or high-risk plaques remains a major challenge in the treatment of CAD. Recently, growing evidence shows that DNA damage plays a role in the initiation and progression of atherosclerotic plaque. Cytokinesis-block micronucleus (CBMN) assay is one of the most frequently used and validated method for assessing chromosomal damage and genetic instability. Accordingly, the purpose of this systematic review was to retrieve and discuss existing literature on the studies assessing the association between MN and angiographically-proven CAD. A total of 8 studies published between 2001 and 2017 were included in the meta-analysis. Despite a large heterogeneity between studies (I= 99.7 %, p < 0.0001), an overall increase of MN frequencies was found in patients with CAD compared with control group (meta-MR = 1.96; 95 % CI, 1.5-3.2, p = 0.009). A subgroup analysis showed an increase in the frequency of MN formation for both two- vessel (MR = 2.13, 95 % CI: 0.9-6.9, p = 0.08) and three-vessel disease (MR = 2.89, 95 % CI: 1.84-4.55, P = 0.06). Overall, the results of this meta-analysis provide evidence of an association between CBMN and presence, extent and severity of angiographically-assessed CAD. However, the small number of papers analyzed requires further large and more rigorously designed studies, carefully considering a series of clinical confounding factors, such as the quality of the metabolic control, the influence of drugs and radiation imaging treatments.
Topics: Animals; Coronary Artery Disease; Cytokinesis; DNA Damage; Humans; Micronuclei, Chromosome-Defective; Micronucleus Tests
PubMed: 34083055
DOI: 10.1016/j.mrrev.2020.108348 -
Mutation Research. Reviews in Mutation... 2021Respiratory tissues are highly susceptible to diseases due to the constant exposure to physical and chemical airborne pollutants. Chronic obstructive pulmonary disease...
Respiratory tissues are highly susceptible to diseases due to the constant exposure to physical and chemical airborne pollutants. Chronic obstructive pulmonary disease (COPD) and lung cancer are among the most common causes of serious illness and death worldwide. The inflammatory environment associated with these respiratory diseases has long been accepted as the major player in the development of airway abnormalities. The presence and relevance of DNA damage and genomic instability makes the micronucleus assay a suitable candidate to quantitatively estimate these early pathogenetic events. A systematic review and meta-analysis were planned to determine underlying common mechanisms that can explain the relationships between COPD and lung cancer. A total of 17 studies from Jan 1999 to Dec 2019 comparing micronucleus frequency in patients affected by respiratory diseases vs healthy controls were analysed. Our results confirmed the presence of significant association between MN frequency and the diseases investigated, and suggested a circle of events linking inflammation induced oxidative stress to the risk of disease through genomic instability and hypoxia. Therefore, using non-invasive, robust and cost effective genomic instability assays such as the micronucleus assay, would allow us to capture unique phenotypic and biological changes that would allow the identification of subjects at high risk of developing lung diseases and improve early detection strategies.
Topics: Animals; Genomic Instability; Humans; Inflammation; Lung Neoplasms; Micronucleus Tests; Oxidative Stress; Pulmonary Disease, Chronic Obstructive
PubMed: 34083053
DOI: 10.1016/j.mrrev.2020.108344 -
Mutation Research. Reviews in Mutation... 2021A systematic review and a meta-analysis were performed on 19 studies on head and neck cancer (HNC) and 21 studies on breast cancer (BC) to evaluate the application of... (Meta-Analysis)
Meta-Analysis
A systematic review and a meta-analysis were performed on 19 studies on head and neck cancer (HNC) and 21 studies on breast cancer (BC) to evaluate the application of micronucleus (MN) assay as a predictive and prognostic test for cancer risk. In these studies the MN test was applied in peripheral lymphocytes and buccal cells of patients and healthy subjects with family history of cancer. The meta-analysis on MN applied in buccal cells of HNC patients was performed on two subgroups of studies. A significant increase of MN frequency in patients compared to healthy controls was observed for the subgroup on oral cancer (243 cases/370 controls, meta-MR = 4.71 95 %CI:2.75-8.06) and HNC (204 patients/163 controls metaMR=2.28 95 %CI:2.02-2.58). A metaMR = 3.27 (95 %CI:1.41-7.59) was obtained for MN applied in peripheral lymphocytes on HNC (160 cases/160 controls). For BC, the analysis of MN in peripheral lymphocytes showed significantly higher values in patients (n = 761) than in controls (n = 788) (meta-MR1.90 95 % CI:1.44-2.49). No statistically significant increase of baseline MN was detected in studies on groups of healthy subjects with BC family history (n = 224) or with BRCA1/2 mutations (n = 101) with respect to the controls. After ex-vivo challenge with ionizing radiation, the meta-analysis revealed a slightly statistically significant increase in MN only in BC patients (n = 614) compared to controls (n = 622)(meta-MR = 1.11 95 %CI:1.02-1.21); no increase was observed in healthy subjects with BC family history carrying or not BRCA1/2 mutations. Significant difference between BC patients (n = 183) and controls (n = 165) was observed by the meta-analysis of data on MN in buccal cells (MR = 3.89 95 %CI:1.54-9.78). The MN assay in buccal cells has some perspective of clinical application in HNC.
Topics: Female; Humans; Breast Neoplasms; Head and Neck Neoplasms; Micronucleus Tests; Mouth Neoplasms
PubMed: 34083052
DOI: 10.1016/j.mrrev.2020.108358 -
Mutation Research. Reviews in Mutation... 2021Approximately 165,000 and 311,000 individuals die annually from urothelial (UC) and cervical (CC) cancer. The therapeutic success of these cancers depends strongly on...
Approximately 165,000 and 311,000 individuals die annually from urothelial (UC) and cervical (CC) cancer. The therapeutic success of these cancers depends strongly on their early detection and could be improved by use of additional diagnostic tools. We evaluated the current knowledge of the use of micronucleus (MN) assays (which detect structural and numerical chromosomal aberrations) with urine- (UDC) and cervix-derived (CDC) cells for the identification of humans with increased risks and for the diagnosis of UC and CC. Several findings indicate that MN rates in UDC are higher in individuals with inflammation and schistosomiasis that are associated with increased prevalence of UC; furthermore, higher MN rates were also found in CDC in women with HPV, Candidiasis and Trichomonas infections which increase the risks for CC. Only few studies were published on MN rates in UDS in patients with UC, two concern the detection of recurrent bladder tumors. Strong correlations were found in individuals with abnormal CC cells that are scored in Pap tests and histopathological abnormalities. In total, 16 studies were published which concerned these topics. MN rates increased in the order: inflammation < ASC-US/ASC-H < LSIL < HSIL < CC. It is evident that MNi numbers increase with the risk to develop CC and with the degree of malignant transformation. Overall, the evaluation of the literature indicates that MNi are useful additional biomarkers for the prognosis and detection of CC and possibly also for UC. In regard to the diagnosis/surveillance of UC, further investigations are needed to draw firm conclusions, but the currently available data are promising. In general, further standardization of the assays is needed (i.e. definition of optimal cell numbers and of suitable stains as well as elucidation of the usefulness of parameters reflecting cytotoxicity and mitotic activity) before MN trials can be implemented in routine screening.
Topics: Cell Transformation, Neoplastic; DNA Damage; Female; Humans; Micronucleus Tests; Urothelium; Uterine Cervical Neoplasms
PubMed: 34083051
DOI: 10.1016/j.mrrev.2020.108361 -
Mutation Research. Reviews in Mutation... 2021Chronic diseases such as cardiovascular diseases, type 2 diabetes or cancer are the global leading cause of mortality. Lifestyle interventions are most effective in...
Impact of dietary and lifestyle interventions in elderly or people diagnosed with diabetes, metabolic disorders, cardiovascular disease, cancer and micronutrient deficiency on micronuclei frequency - A systematic review and meta-analysis.
Chronic diseases such as cardiovascular diseases, type 2 diabetes or cancer are the global leading cause of mortality. Lifestyle interventions are most effective in reducing metabolic risk factors, disease progression or even side effects of a disease. They are also contributing to decelerate the aging process. Genome instability is very often associated with aging or the above-mentioned diseases, and triggered by inflammation and oxidative stress. An established method to measure chromosomal damage is the cytokinesis block micronucleus (CBMN) cytome assay. The aim of this review and meta-analysis is to collect and analyse the current literature regarding the effects of a lifestyle based (dietary) intervention on changes of micronuclei (MNi), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) in elderly subjects or people diagnosed with diabetes, metabolic disorders, cardiovascular disease, cancer or micronutrient deficiency. Although the main important diseases were considered as well as the large topic of aging, the number and methodological quality in terms of samples size, duration and rationale of the intervention or an inclusion of a control group of available intervention studies with these backgrounds was low. Most of the studies used antioxidant vitamins or folate, few investigated the whole diet. Only one study showed a physical activity intervention approach. The interventions did not lead to decreased genomic marker despite a few cancer related studies, where particularly MN frequency in mucosa lesions and leukoplakia was reduced by green tea and antioxidants. The performed meta-analysis of the available RCTs did not show a significant reduction of MNi, NBUDs or NPBs of most of the interventions performed, except for green tea. Data show in general a lack of an appropriate number of sound lifestyle based intervention studies linking cytogenetic damage and chronic diseases.
Topics: Cardiovascular Diseases; DNA Damage; Diabetes Mellitus; Humans; Metabolic Diseases; Micronucleus Tests; Neoplasms
PubMed: 34083034
DOI: 10.1016/j.mrrev.2021.108367 -
Mutation Research. Reviews in Mutation... 2020Auto-immune diseases (AUD) are characterized by an immune response to antigenic components of the host itself. The etiology of AUD is not well understood. The available... (Meta-Analysis)
Meta-Analysis
Auto-immune diseases (AUD) are characterized by an immune response to antigenic components of the host itself. The etiology of AUD is not well understood. The available evidence points to an interaction between genetic, epigenetic, environmental, infectious and life-style factors. AUD are more prevalent in women than in men; sex hormones play a crucial role in this sex bias. Micronuclei (MN) emerged as a new player in the induction of AUD, based on the capacity of DNA-sensors to detect self-DNA that leaks into the cytoplasm from disrupted MN and induce the cGAS-STING pathway triggering an innate auto-immune response and chronic inflammation. It was found that inflammation can induce MN and MN can induce inflammation, leading to a vicious inflammation-oxidative-DNA damage-MN-formation-chromothripsis cycle. MN originating from sex chromosome-loss may induce inflammation and AUD. We performed a systematic review of studies reporting MN in patients with systemic or organ-specific AUD. A meta-analysis was performed on lymphocyte MN in diabetes mellitus (10 studies, 457 patients/290 controls) and Behcet's disease (3 studies, 100 patients/70 controls) and for buccal MN in diabetes mellitus (11 studies, 507 patients/427 controls). A statistically significant increase in patients compared to controls was found in the meta-analyses providing an indication of an association between MN and AUD. A 36%-higher mean-MRi in buccal cells (3.8+/-0.7) was found compared to lymphocytes (2.8+/-0.7)(P = 0.01). The meta-MRi in lymphocytes and buccal cells (1.7 and 3.0 respectively) suggest that buccal cells may be more sensitive. To assess their relative sensitivity, studies with measurements from the same subjects would be desirable. It is important that future studies (i) investigate, in well-designed powered studies, the prospective association of MN-formation with AUD and (ii) explore the molecular mechanisms by which chromosome shattering in MN and the release of chromatin fragments from MN lead to the formation of auto-antibodies.
Topics: Autoimmune Diseases; Chromothripsis; Female; Humans; Inflammation; Lymphocytes; Male; Micronuclei, Chromosome-Defective; Micronucleus Tests
PubMed: 33339583
DOI: 10.1016/j.mrrev.2020.108335 -
Mutation Research. Reviews in Mutation... 2020The Ames test has become one of the most commonly used tests to assess the mutagenic potential of medicinal plants since they have several biological activities and thus...
The Ames test has become one of the most commonly used tests to assess the mutagenic potential of medicinal plants since they have several biological activities and thus have been used in traditional medicine and in the pharmaceutical industry as a source of raw materials. Accordingly, this review aims to report previous use of the Ames test to evaluate the mutagenic potential of medicinal plants. A database was constructed by curating literature identified by a search on the electronic databases Medline (via Pubmed), Science Direct, Scopus, and Web of Science from 1975 to April 2020, using the following terms: "genotoxicity tests" OR "mutagenicity tests" OR "Ames test" AND "medicinal plants." From the research, 239 articles were selected, including studies of 478 species distributed across 111 botanical families, with Fabaceae, Asteraceae and Lamiaceae being the most frequent. It was identified that 388 species were non-mutagenic. Of these, 21% (83/388) showed antimutagenic potential, most notable in the Lamiaceae family. The results also indicate that 18% (90/478) of the species were mutagenic, of which 54% were mutagenic in the presence and absence of S9. Strains TA98 and TA100 showed a sensitivity of 93% in detecting plant extracts with mutagenic potential. However, the reliability of many reviewed studies regarding the botanical extracts may be questioned due to technical issues, such as testing being performed only in the presence or absence of S9, use of maximum doses below 5 mg/plate and lack of information on the cytotoxicity of tested doses. These methodological aspects additionally demonstrated that a discussion about the doses used in research on mixtures, such as the ones assessed with botanical extracts and the most sensitive strains employed to detect the mutagenic potential, should be included in a possible update of the guidelines designed by the regulatory agencies.
Topics: Humans; Medicine, Traditional; Microsomes; Mutagenicity Tests; Mutagens; Plants, Medicinal; Salmonella
PubMed: 33339578
DOI: 10.1016/j.mrrev.2020.108338